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Figure.
Odds Ratios and 95% CIs for the Adjusted Risk of 1-Year Major Adverse Cardiac Events
Odds Ratios and 95% CIs for the Adjusted Risk of 1-Year Major Adverse Cardiac Events

MI indicates myocardial infarction; TVR, target vessel revascularization.

Table 1.  
Baseline Clinical, Lesion, and Procedural Characteristics
Baseline Clinical, Lesion, and Procedural Characteristics
Table 2.  
Social and Behavioral Determinants of Health in PD Study Cohort
Social and Behavioral Determinants of Health in PD Study Cohort
Table 3.  
Clinical Outcomes of Major Adverse Cardiovascular Events at 12 Months
Clinical Outcomes of Major Adverse Cardiovascular Events at 12 Months
Table 4.  
Independent Predictors of Death/MI/TVR
Independent Predictors of Death/MI/TVR
1.
 2014 National population projections tables. United States Census Bureau. https://www.census.gov/data/tables/2014/demo/popproj/2014-summary-tables.html. Accessed September 11, 2017.
2.
Melloni  C, Berger  JS, Wang  TY,  et al.  Representation of women in randomized clinical trials of cardiovascular disease prevention.  Circ Cardiovasc Qual Outcomes. 2010;3(2):135-142.PubMedGoogle ScholarCrossref
3.
 Collection of race and ethnicity data in clinical trials. US Food and Drug Administration. https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126396.pdf. Accessed September 11, 2017.
4.
 NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research: amended, October, 2001. National Institutes of Health. https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. Accessed September 11, 2017.
5.
 Leading causes of death in males and females, United States. Centers for Disease Control and Prevention. https://www.cdc.gov/healthequity/lcod/index.htm. Accessed September 11, 2017.
6.
Maas  AH, van der Schouw  YT, Regitz-Zagrosek  V,  et al.  Red alert for women’s heart: the urgent need for more research and knowledge on cardiovascular disease in women: proceedings of the workshop held in Brussels on gender differences in cardiovascular disease, 29 September 2010.  Eur Heart J. 2011;32(11):1362-1368.PubMedGoogle ScholarCrossref
7.
Mody  P, Gupta  A, Bikdeli  B, Lampropulos  JF, Dharmarajan  K.  Most important articles on cardiovascular disease among racial and ethnic minorities.  Circ Cardiovasc Qual Outcomes. 2012;5(4):e33-e41.PubMedGoogle ScholarCrossref
8.
Argulian  E, Patel  AD, Abramson  JL,  et al.  Gender differences in short-term cardiovascular outcomes after percutaneous coronary interventions.  Am J Cardiol. 2006;98(1):48-53.PubMedGoogle ScholarCrossref
9.
Thompson  CA, Kaplan  AV, Friedman  BJ,  et al.  Gender-based differences of percutaneous coronary intervention in the drug-eluting stent era.  Catheter Cardiovasc Interv. 2006;67(1):25-31.PubMedGoogle ScholarCrossref
10.
Lansky  AJ, Costa  RA, Mooney  M,  et al; TAXUS-IV Investigators.  Gender-based outcomes after paclitaxel-eluting stent implantation in patients with coronary artery disease.  J Am Coll Cardiol. 2005;45(8):1180-1185.PubMedGoogle ScholarCrossref
11.
Akhter  N, Milford-Beland  S, Roe  MT, Piana  RN, Kao  J, Shroff  A.  Gender differences among patients with acute coronary syndromes undergoing percutaneous coronary intervention in the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR).  Am Heart J. 2009;157(1):141-148.PubMedGoogle ScholarCrossref
12.
Collins  SD, Torguson  R, Gaglia  MA  Jr,  et al.  Does black ethnicity influence the development of stent thrombosis in the drug-eluting stent era?  Circulation. 2010;122(11):1085-1090.PubMedGoogle ScholarCrossref
13.
Batchelor  WB, Ellis  SG, Ormiston  JA,  et al.  Racial differences in long-term outcomes after percutaneous coronary intervention with paclitaxel-eluting coronary stents.  J Interv Cardiol. 2013;26(1):49-57.PubMedGoogle ScholarCrossref
14.
Stefanini  GG, Baber  U, Windecker  S,  et al.  Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials.  Lancet. 2013;382(9908):1879-1888.PubMedGoogle ScholarCrossref
15.
Kandzari  DE, Amjadi  N, Caputo  C,  et al.  One-year outcomes in “real-world” patients treated with a thin-strut, platinum-chromium, everolimus-eluting stent (from the PROMUS Element Plus US Post-Approval Study [PE-Plus PAS]).  Am J Cardiol. 2016;117(4):539-545.PubMedGoogle ScholarCrossref
16.
World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.  JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053.Google ScholarCrossref
17.
Meredith  IT, Whitbourn  R, Scott  D,  et al.  PLATINUM QCA: a prospective, multicentre study assessing clinical, angiographic, and intravascular ultrasound outcomes with the novel platinum chromium thin-strut PROMUS Element everolimus-eluting stent in de novo coronary stenoses.  EuroIntervention. 2011;7(1):84-90.PubMedGoogle ScholarCrossref
18.
Stone  GW, Teirstein  PS, Meredith  IT,  et al; PLATINUM Trial Investigators.  A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: the PLATINUM (a Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of Up to Two de Novo Coronary Artery Lesions) trial.  J Am Coll Cardiol. 2011;57(16):1700-1708.PubMedGoogle ScholarCrossref
19.
Coakley  M, Fadiran  EO, Parrish  LJ, Griffith  RA, Weiss  E, Carter  C.  Dialogues on diversifying clinical trials: successful strategies for engaging women and minorities in clinical trials.  J Womens Health (Larchmt). 2012;21(7):713-716.PubMedGoogle ScholarCrossref
20.
Resnik  DB, Jones  CW.  Research subjects with limited English proficiency: ethical and legal issues.  Account Res. 2006;13(2):157-177.PubMedGoogle ScholarCrossref
21.
Nolan  MR, Nguyen  T-L.  Analysis and reporting of sex differences in phase III medical device clinical trials-how are we doing?  J Womens Health (Larchmt). 2013;22(5):399-401.PubMedGoogle ScholarCrossref
22.
Pinnow  E, Herz  N, Loyo-Berrios  N, Tarver  M.  Enrollment and monitoring of women in post-approval studies for medical devices mandated by the Food and Drug Administration.  J Womens Health (Larchmt). 2014;23(3):218-223.PubMedGoogle ScholarCrossref
23.
Dhruva  SS, Bero  LA, Redberg  RF.  Gender bias in studies for Food and Drug Administration premarket approval of cardiovascular devices.  Circ Cardiovasc Qual Outcomes. 2011;4(2):165-171.PubMedGoogle ScholarCrossref
24.
 FDASIA section 907: inclusion of demographic subgroups in clinical trials. US Food and Drug Administration. https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm389100.htm. Accessed September 11, 2017.
25.
Berger  JS, Melloni  C, Wang  TY,  et al.  Reporting and representation of race/ethnicity in published randomized trials.  Am Heart J. 2009;158(5):742-747.PubMedGoogle ScholarCrossref
26.
Kurt  A, Semler  L, Meyers  M, Porter  BG, Jacoby  JL, Stello  B.  Research professionals’ perspectives, barriers, and recommendations regarding minority participation in clinical trials [published online December 21, 2016].  J Racial Ethn Heal Disparities.Google Scholar
27.
Pradhan  J, Schreiber  TL, Niraj  A,  et al.  Comparison of five-year outcome in African Americans versus Caucasians following percutaneous coronary intervention.  Catheter Cardiovasc Interv. 2008;72(1):36-44.PubMedGoogle Scholar
28.
Gaglia  MAJ  Jr, Steinberg  DH, Pinto Slottow  TL,  et al.  Racial disparities in outcomes following percutaneous coronary intervention with drug-eluting stents.  Am J Cardiol. 2009;103(5):653-658.PubMedGoogle ScholarCrossref
29.
Kobayashi  T, Glorioso  TJ, Armstrong  EJ,  et al.  Comparative outcomes after percutaneous coronary intervention among black and white patients treated at US Veterans Affairs hospitals [published online July 19, 2017].  JAMA Cardiol. PubMedGoogle Scholar
30.
Kumar  RS, Douglas  PS, Peterson  ED,  et al.  Effect of race and ethnicity on outcomes with drug-eluting and bare metal stents: results in 423 965 patients in the linked National Cardiovascular Data Registry and centers for Medicare & Medicaid services payer databases.  Circulation. 2013;127(13):1395-1403.PubMedGoogle ScholarCrossref
31.
Gurbel  PA, Bliden  KP, Cohen  E,  et al.  Race and sex differences in thrombogenicity: risk of ischemic events following coronary stenting.  Blood Coagul Fibrinolysis. 2008;19(4):268-275.PubMedGoogle ScholarCrossref
32.
Mehran  R, Baber  U, Steg  PG,  et al.  Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study.  Lancet. 2013;382(9906):1714-1722.PubMedGoogle ScholarCrossref
33.
Awad  HH, Anderson  FA  Jr, Gore  JM, Goodman  SG, Goldberg  RJ.  Cardiogenic shock complicating acute coronary syndromes: insights from the Global Registry of Acute Coronary Events.  Am Heart J. 2012;163(6):963-971.PubMedGoogle ScholarCrossref
34.
Garot  P, Morice  MC, Tresukosol  D,  et al; LEADERS FREE Investigators.  2-Year outcomes of high bleeding risk patients after polymer-free drug-coated stents.  J Am Coll Cardiol. 2017;69(2):162-171.PubMedGoogle ScholarCrossref
35.
Gupta  R, Kirtane  AJ, Ozane  MO,  et al.  Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents in subjects with peripheral arterial disease: analysis from the ADAPT-DES Study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).  Circ Cardiovasc Interv. 2017;10(3):.Google Scholar
36.
Kang  J, Park  KW, Han  JK,  et al.  Usefulness of the baseline syntax score to predict 3-year outcome after complete revascularization by percutaneous coronary intervention.  Am J Cardiol. 2016;118(5):641-646.PubMedGoogle ScholarCrossref
37.
Kunadian  V, Qiu  W, Ludman  P,  et al; National Institute for Cardiovascular Outcomes Research.  Outcomes in patients with cardiogenic shock following percutaneous coronary intervention in the contemporary era: an analysis from the BCIS database (British Cardiovascular Intervention Society).  JACC Cardiovasc Interv. 2014;7(12):1374-1385.PubMedGoogle ScholarCrossref
38.
Lee  JM, Kang  J, Lee  E,  et al.  Chronic kidney disease in the second-generation drug-eluting stent era: pooled analysis of the Korean multicenter drug-eluting stent registry.  JACC Cardiovasc Interv. 2016;9(20):2097-2109.PubMedGoogle ScholarCrossref
39.
Lee  SY, Hong  MK, Shin  DH,  et al.  Association between duration of dual antiplatelet therapy and angiographic multivessel disease on outcomes in patients treated with newer-generation drug-eluting stents.  Circ Cardiovasc Interv. 2016;9(11):e004256.PubMedGoogle ScholarCrossref
40.
Secemsky  EA, Yeh  RW, Kereiakes  DJ,  et al; Dual Antiplatelet Therapy Study Investigators.  Extended duration dual antiplatelet therapy after coronary stenting among patients with peripheral arterial disease: a subanalysis of the Dual Antiplatelet Therapy Study.  JACC Cardiovasc Interv. 2017;10(9):942-954.PubMedGoogle ScholarCrossref
41.
Elwert  F, Christakis  NA.  The effect of widowhood on mortality by the causes of death of both spouses.  Am J Public Health. 2008;98(11):2092-2098.PubMedGoogle ScholarCrossref
42.
Moon  JR, Kondo  N, Glymour  MM, Subramanian  SV.  Widowhood and mortality: a meta-analysis.  PLoS One. 2011;6(8):e23465.PubMedGoogle ScholarCrossref
43.
Gaglia  MA  Jr, Torguson  R, Xue  Z,  et al.  Effect of insurance type on adverse cardiac events after percutaneous coronary intervention.  Am J Cardiol. 2011;107(5):675-680.PubMedGoogle ScholarCrossref
44.
Krueger  KP, Berger  BA, Felkey  B.  Medication adherence and persistence: a comprehensive review.  Adv Ther. 2005;22(4):313-356.PubMedGoogle ScholarCrossref
45.
Haynes  RB, McDonald  H, Garg  AX, Montague  P.  Interventions for helping patients to follow prescriptions for medications.  Cochrane Database Syst Rev. 2002;(2):CD000011.PubMedGoogle Scholar
46.
Cote  CL, Singh  S, Yip  AM,  et al.  Increased distance from the tertiary cardiac center is associated with worse 30-day outcomes after cardiac operations.  Ann Thorac Surg. 2015;100(6):2213-2218.PubMedGoogle ScholarCrossref
47.
Victoor  A, Delnoij  DM, Friele  RD, Rademakers  JJ.  Determinants of patient choice of healthcare providers: a scoping review.  BMC Health Serv Res. 2012;12(1):272.PubMedGoogle ScholarCrossref
48.
Palacio  AM, Uribe  C, Hazel-Fernandez  L,  et al.  Can phone-based motivational interviewing improve medication adherence to antiplatelet medications after a coronary stent among racial minorities? a randomized trial.  J Gen Intern Med. 2015;30(4):469-475.PubMedGoogle ScholarCrossref
49.
Free  C, Phillips  G, Watson  L,  et al.  The effectiveness of mobile-health technologies to improve health care service delivery processes: a systematic review and meta-analysis.  PLoS Med. 2013;10(1):e1001363.PubMedGoogle ScholarCrossref
50.
Lefebvre  RC, Bornkessel  AS.  Digital social networks and health.  Circulation. 2013;127(17):1829-1836.PubMedGoogle ScholarCrossref
Original Investigation
December 2017

Outcomes in Women and Minorities Compared With White Men 1 Year After Everolimus-Eluting Stent Implantation: Insights and Results From the PLATINUM Diversity and PROMUS Element Plus Post-Approval Study Pooled Analysis

Author Affiliations
  • 1Tallahassee, Memorial Healthcare, Tallahassee, Florida
  • 2Piedmont Heart Institute, Atlanta, Georgia
  • 3Baptist Hospital, Little Rock, Arizona
  • 4Research Physicians Network Alliance, Hollywood, Florida
  • 5MedStar Union Memorial Hospital, Baltimore, Maryland
  • 6North Carolina Heart and Vascular Research, Raleigh
  • 7Seton Heart Institute, Austin, Texas
  • 8Cardiovascular Institute of Northwest Florida, Panama City
  • 9Central Cardiology Medical Clinic, Bakersfield, California
  • 10Charlotte Heart and Vascular Institute, Port Charlotte, Florida
  • 11Baystate Medical Center, Springfield, Massachusetts
  • 12University of Iowa Carver College of Medicine, Iowa City
  • 13Mount Sinai Medical Center, New York, New York
  • 14Boston Scientific Corporation, Marlborough, Massachusetts
JAMA Cardiol. 2017;2(12):1303-1313. doi:10.1001/jamacardio.2017.3802
Key Points

Question  Are 1-year outcomes among women and minorities different from white men after contemporary percutaneous coronary intervention, and what are the predictors?

Findings  In this pooled analysis study, women and minorities had more baseline comorbidities. After risk adjustment, 1-year major adverse cardiovascular events (death/myocardial infarction/target vessel revascularization), were not significantly different between groups; however, women and minorities had a higher adjusted risk of death/myocardial infarction than white men primarily because of a greater hazard of nonstent-related myocardial infarctions.

Meaning  Contemporary everolimus-eluting stents confer similar risks of major adverse cardiovascular events across race/ethnicity and sex; however, there remains opportunity to reduce an incremental risk of recurrent nonstent-related ischemic events in women and minority patients after percutaneous coronary intervention.

Abstract

Importance  There exist limited outcomes data for women and minorities after contemporary percutaneous coronary intervention (PCI).

Objective  To examine 1-year outcomes in women and minorities vs white men after PCI with everolimus-eluting stents.

Design, Settings, and Participants  The PLATINUM Diversity study was a single-arm study enrolling women and minorities. Patient-level pooling with the PROMUS Element Plus Post-Approval Study was prespecified. Data on social determinants of health and language were collected in the PLATINUM Diversity cohort, which included 1501 patients at 52 US sites. The PROMUS Element Plus Post-Approval study enrolled 2681 patients at 52 US sites with some site overlap and included an “all-comers” population. All patients were enrolled beginning in October 2014 and were followed for 12 months. Analyses began in August 2016.

Interventions  Patients received 1 or more everolimus-eluting stent implantation.

Main Outcomes and Measures  The primary end point was 1-year major adverse cardiac events (MACE), which included death/myocardial infarction (MI)/target vessel revascularization. Secondary ischemic end points were also evaluated.

Results  The pooled study consisted of 4182 patients: 1635 white men (39.1%), 1863 women (white and minority) (44.5%), and 1059 minority patients (women and men) (25.3%). Women and minorities had a higher prevalence of diabetes, prior stroke, hypertension, renal disease, and congestive heart failure than white men but lower rates of multivessel disease, prior coronary artery bypass graft surgery, prior MI, and smoking. Unadjusted 1-year MACE rates (white men, 7.6%; women, 8.6%; minorities, 9.6%) were similar between groups with no significant differences after risk adjustment. The adjusted risk of death/MI was higher among women (odds ratio, 1.6; 95% CI, 1.1-2.4) and minorities (odds ratio, 1.9; 95% CI, 1.2-2.8) compared with white men and the adjusted risk of MI was higher in minorities (odds ratio, 2.6; 95% CI, 1.4-4.8). These differences were driven primarily by nonstent-related MIs. Within the PLATINUM Diversity cohort, the independent predictors of MACE were cardiogenic shock, renal disease, history of peripheral vascular disease, multivessel disease, widowhood, and lack of private insurance.

Conclusions and Relevance  After contemporary everolimus-eluting stent implantation, women and minorities experience a similar risk of 1-year MACE but a higher adjusted risk of recurrent ischemic events primarily because of nonstent-related MIs. Both clinical and angiographic factors and social determinants of health, including widowhood and insurance status, contribute to 1-year MACE among women and minorities.

Introduction

With minorities expected to represent more than half of the population by 2060, the United States is becoming increasingly diverse.1 Despite these trends, cardiovascular clinical trials have continued to include predominantly white men.2 This enrollment bias persists despite major efforts from the US Food and Drug Administration and the National Institutes of Health to improve clinical trial diversity.2-4 Given that cardiovascular disease remains the leading cause of death in men and women regardless of race/ethnicity,5 broad clinical trial inclusion is pivotal to providing an adequate evidence base from which new therapies may be assessed.

Women and minorities often present with more comorbidities than white men, thereby potentially contributing to differential outcomes.6-8 Some, but not all, studies have shown a higher likelihood of postpercutaneous coronary intervention (PCI) adverse events in women, while others have reported higher risks in minorities.8-14 However, these studies have yielded conflicting results and have been limited by outdated stent technologies, small sample sizes, short duration of follow-up, retrospective study designs, or have been devoid of angiographic data and/or insight into the effect of social determinants of health (SDOH).

The purpose of our study is to compare the baseline clinical, angiographic, and procedural characteristics and 1-year contemporary PCI outcomes of women and minorities with that of white men and explore the effect of SDOH.

Methods
Study Design, Setting, and Participants

The PLATINUM Diversity Study (PD) was a prospective, multicenter, open-label observational study that enrolled patients who received 1 or more everolimus-eluting stent and self-identified as having at least 1 of the following characteristics: female sex, black (of African heritage), Hispanic/Latino, or American Indian/Alaskan Native. There were no exclusion criteria. Patients were enrolled at 52 US sites beginning in October 2014 and followed for 12 months. Social determinants of health, including access to and use of health care, living circumstances, socioeconomic status, exercise habits, alcohol and drug use, and language barriers were collected prospectively in the PD study.

The PROMUS Element Plus Post-Approval Study (PE Plus) was a prospective, multicenter, open-label observational study completed in August 2014 that enrolled an “all-comers” cohort of patients across 52 US sites who were treated with an everolimus-eluting stent.15

The PD and PE Plus studies complied with the Declaration of Helsinki16 and were approved by each site’s locally appointed ethics committee. Written informed consent was required within 24 hours of stent implantation within both studies. Analyses began in August 2016. The PD and PE Plus studies are registered at http://www.clinicaltrials.gov under identifiers NCT02240810 and NCT01589978, respectively.

Device Description

The everolimus-eluting stents used in the PD and PE Plus studies are thin-strut platinum chromium everolimus-eluting stents with a permanent polyvinylidene fluoride-co-hexafluoropropene polymer. Some of these stents had additional connectors within the proximal stent segments. These stents have demonstrated consistent safety and performance across the PD clinical trial program and in PE Plus .15,17,18

End Points

The primary end point was the incidence of 1-year major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR). Additional secondary end points analyzed at 1 year included death (cardiac and noncardiac), death/MI, MI (stent-related and nonstent-related), Academic Research Consortium definite/probable stent thrombosis, and target vessel failure. All end points were adjudicated by an independent clinical events committee using established definitions from the PD and PE Plus studies.15,17,18

Statistical Methods

Outcomes were compared between women vs white men and minorities vs white men, respectively. Two-sided t tests were used to compare continuous variables and χ2 or Fisher exact tests were used for discrete variables. A χ2 test compared the unadjusted outcomes between minority patients (black, Hispanic/Latino, and American Indian/Alaskan native) from the pooled cohort and white men from PE Plus. A similar method compared women from the pooled cohort and white men from PE Plus. Statistical significance was declared if the 2-sided lower 95% CI boundary on the difference between groups was less than 0 and the χ2P value was less than .05. Given the 284 minority and 806 female patients enrolled in PE Plus and a 7.3% 1-year MACE rate noted in the 1635 white men from PE Plus, we estimated that we would need 1500 women and minority patients in PD (assuming 5% attrition) to achieve more than 80% power to detect at least a 3% difference in MACEs. An assessment of the poolability of patients across PD and PE Plus sites was made by fitting a logistic regression model (eTable 1 in the Supplement).

Odds ratios (OR) and 95% CIs for the adjusted risk of 1-year MACE were generated using multivariate logistic regression. Baseline clinical, angiographic, and procedural characteristics were entered in the model (Figure). Covariates with a univariate P value of less than .10 were selected to remain in the model. To risk adjust, a group variable (white men vs women or vs minority patients) was forced into the model and the OR determined.

We first built a multivariate model predicting MACE from the entire pooled study sample. For women and minorities enrolled only in the PD cohort, we also created a separate model for MACE, including the SDOH data that were collected in this group. All statistical analyses were performed using SAS software, version 9.2 or later (SAS Institute Inc).

Results
Participants and Enrollment

The study consisted of 4182 patients, including 1501 enrolled in the PD study and 2681 from the PE Plus study. The distribution of patients by race/ethnicity and sex and patient flow are shown in eFigure 1 and eFigure2 in the Supplement. The final pooled sample included 1635 white men (39.1%), 1863 women (white and minority) (44.5%), and 1059 minority patients (women and men) (25.3%).

Baseline Characteristics

Baseline characteristics are shown in Table 1. Compared with white men, women were older and had a higher prevalence of diabetes, hypertension, history of congestive heart failure, prior transient ischemic attack/cerebrovascular accident, renal disease, and lower rates of prior MI, multivessel disease, prior PCI, and prior coronary artery bypass graft surgery. Minority patients were slightly younger and had a higher prevalence of diabetes, hypertension, prior congestive heart failure, prior cerebrovascular accident, and renal disease and a lower prevalence of hyperlipidemia, family history of coronary artery disease, prior MI, prior coronary artery bypass graft surgery, atrial fibrillation, and multivessel disease. The prevalence of diabetes was highest among minority patients (535 of 1059 [50.5%]) followed by women (790 of 1863 [42.4%]) and white men (561 of 1635 [34.3%]). Minorities had nearly half the rate of preexisting atrial fibrillation (54 of 1059 [5.1%]) as white men (163 of 1635 [10.0%]) and women (171 of 1863 [9.2%]). Women and minorities were less likely to experience angina and women less likely to have silent ischemia than white men. Mean left ventricular ejection fraction was normal (>50%) in all groups, although slightly higher in women and slightly lower in minorities compared with white men.

Women and minorities had slightly smaller reference vessel diameter and a higher prevalence of moderate-to-severe lesion calcification and chronic total occlusions compared with white men. Women and white men shared similar lesion and stent lengths, with slightly longer lengths observed in minority patients. The prevalence of bifurcation lesions was highest in white men, whereas women had the highest prevalence of ostial lesions. Intravascular ultrasonography before stenting was performed at a similar rate across groups; however, intravascular ultrasonography after stenting was used more frequently among women and minorities. The use of fractional flow reserve testing was highest in minority patients. Women and minorities were treated with postdilation less often than white men. There were no differences between groups in the rate of urgent/emergent interventions and the number of lesions treated per patient.

The rate of aspirin and dual antiplatelet therapy (DAPT) use was slightly but significantly lower in women and minorities compared with white men (eFigure 3 in the Supplement). Dual antiplatelet therapy use at 6 and 12 months was 91% and 87%, respectively, for white men; 88% and 85%, respectively, for women; and 86% and 84%, respectively, for minority patients.

Baseline Social Determinants of Health Data in the PD Cohort

Social determinants of health for the PD cohort are shown in Table 2. Because the 2 groups (women and minorities) were not entirely mutually exclusive, P values for comparisons are not provided. Overall, women were older and more likely to have health care insurance and established primary care. For both groups, travel distance and time to the hospital performing the index PCI was significant, although this appeared to be more evident in women, such that nearly 404 of 1501 (26.9%) lived more than 48 km from the hospital. Women were more often retired, widowed, and better educated, while minorities were more often single, either currently employed or unemployed, and not retired. Of 1501 patients, 1056 (70.3%) were living with family. Although rates of nondisclosure of income were high, low income levels were common; 373 of all PD patients (24.9%) reported a household income of less than $25 000. Minorities were more likely than women to possess a smartphone, exercise regularly, and admit to alcohol and substance abuse. Minorities were also more likely to experience patient-physician language discordance.

Unadjusted and Adjusted Clinical Outcomes

The unadjusted primary 1-year MACE rate was similar across groups (white men, 7.6% vs women, 8.6%; [P = .33]; white men vs minorities, 9.6% [P = .08]) (Table 3 and eFigure 4 in the Supplement). Unadjusted rates of death/MI, death, and MI were higher in minority patients compared with white men (death/MI, 6.4% vs 3.1% [P = <.001]; death, 3.7% vs 2.2% [P = .03]; MI, 3.1% vs 1.1% [P = <.001]). Analogously, women had a higher unadjusted rate of death/MI and death than white men (death/MI, 5.0% vs 3.1% [P = .004]; death, 3.4% vs 2.2% [P = .04]) and a trend toward a higher rate of MI (1.9% vs 1.1% [P = .06]). Unadjusted rates of TVR, target vessel failure, and Academic Research Consortium stent thrombosis were similar across all 3 groups.

After multivariate adjustment for imbalances in baseline characteristics, there were no between-group differences in 1-year MACE, death, and TVR (Figure). The risk adjusted rate of death/MI was higher in both women (OR, 1.6; 95% CI, 1.11-2.39; P = .01) and minorities (OR, 1.9; 95% CI, 1.22-2.80; P = .004) compared with white men. Minorities also had a higher adjusted risk of MI (OR, 2.6; 95% CI, 1.40-4.82; P = .002), whereas in women there was only a trend toward a higher risk of MI (OR, 1.7; 95% CI, 0.91-3.09; P = .09). These differences were driven mostly by higher rates of nonstent-related MIs than stent-related events (Table 3). Compared with white men, there was a 2.6- and 5.3-fold higher risk of nonstent-related MI in women and minorities, respectively, with a 1.8-fold higher risk of stent-related MI seen only in minority patients.

Multivariate Predictors of Outcome

The independent predictors of MACE for the entire pooled cohort were renal disease, prior cerebrovascular accident, multivessel disease, prior PCI, history of congestive heart failure, prior MI, and age (Table 4). For the PD cohort (women and minorities) in which SDOH were available, the independent predictors of MACE were cardiogenic shock, renal disease, peripheral vascular disease, multivessel disease, widowed status (vs married or divorced), and lack of private insurance (Table 4).

Discussion

This study was specifically designed to prospectively collect comprehensive PCI outcomes data on women and minorities and compare with white men. We report that (1) with concerted effort and appropriate site selection, women and minorities may be rapidly enrolled in a large, multicenter, national PCI outcomes study with robust follow-up; (2) white men, women, and minorities share comparable adjusted risks of 1-year MACE, death, and TVR; (3) women and minorities appear to encounter higher risks of recurrent ischemic events (death/MI for women and death/MI and MI for minorities) that are driven primarily by nonstent-related MIs and; (4) SDOH, such as marital/widowed status and insurance status, appear to significantly affect outcomes in women and minorities.

Historically, white men have served as the prototypical clinical trial patient with outcomes then extrapolated to others.19 Because women and minorities may respond differently to medical or device interventions, building an adequate database for these underrepresented groups is germane. Impediments to achieving diverse study enrollment include participating site characteristics/location, broad accessibility of women and minorities to trial sites and investigators, willingness of patients to participate, and experience of the research team in obtaining informed consent, especially when English is not the first language.20 To our knowledge, during the last decade, efforts to curb these trends have been unsuccessful.6,21-23 For years, the US Food and Drug Administration has promoted the collection and presentation of data on race/ethnicity and sex in clinical trials.3,23 Section 907 in the Food and Drug Administration Safety and Innovation Act of 201224 resulted in further efforts to refine the conduct and analysis of clinical trials to provide the best estimates of treatment effects in diverse populations. Similarly, the National Institutes of Health requires all funded clinical trials to include adequate enrollment of women and minorities.4 Still, only about a third of cardiovascular clinical trials collect data on race/ethnicity and sex, and, when reported, only 25% to 30% of US study enrollees are women and fewer are minorities.2,25

Using an enriched cohort design for the PD study and pooling with the PE Plus cohort, our study included approximately 50% women and double the usual proportion of minorities. Until existing enrollment biases are eliminated, novel study designs, such as the present study, will be necessary to construct clinical databases more representative of US demographics. Counter to prevailing beliefs and a report suggesting that nonwhite race and patient-physician language discordance serve as impediments to clinical trial enrollment,26 we demonstrate that, with appropriate site selection and concerted effort, women and minorities can be enrolled in a large, national, multicenter PCI outcomes study at a rate comparable with conventional studies. By completing enrollment 6 months ahead of schedule, the PD study enrolled patients faster than PE Plus. We attribute this to the highly motivated nature of our PD sites and their efforts to recruit these patients.

Consistent with prior studies, we observed that women and minorities present with more baseline comorbidities.8-11,27-29 This likely accounts for the higher unadjusted rates of death and MI in these cohorts. However, after risk adjustment, MACE, death, and TVR were comparable between all 3 groups, suggesting that in the era of second generation everolimus-eluting stents, race/ethnicity and sex appear to have little to no effect on these outcomes. These findings contrast with those observed with first generation drug-eluting stents, for which worse outcomes, including death/MI and stent thrombosis, have been reported in black patients.12,13,30 We suspect that advances in stent design (thinner struts and more biocompatible polymers) play an important role in producing uniformly more favorable stent outcomes across race/ethnicity and sex in our study. Despite this, we must acknowledge the higher adjusted risk of death/MI in women and minorities (and MI in minorities) compared with white men. This appeared to be mostly driven by a higher incidence of nonstent-related MIs which, in combination with similar TVR and stent thrombosis rates across groups, argues that stent failure itself contributed minimally to this incremental risk. We suspect that this phenomenon may be instead due to (1) race/ethnicity or sex–related factors that might affect thrombosis or atherosclerosis31; (2) the inability of our model to completely account for measured and/or unmeasured differences in baseline characteristics, including SDOH and; (3) differences in adherence to DAPT. Premature DAPT cessation has been linked to ischemic events.32 Although DAPT use at 6 and 12 months was lower in women and minorities than white men, the small differences observed (2.6% and 3.8% less DAPT use, respectively) probably do not solely account for the 60% and 90% increases, respectively, in the adjusted risk of death/MI. We hypothesize that observed lower DAPT use in women and minorities was due to a higher perceived risk of bleeding and/or concerns about patient nonadherence or cost. Despite the general reassurance that MACE was comparable across all groups, this observed incremental risk of nonstent-related ischemic events in women and minorities was intriguing and merits further investigation.

In addition to traditional clinical and angiographic risk factors, our study evaluated the incremental effect of SDOH on outcomes among women and minorities. The observation that cardiogenic shock, renal disease, peripheral vascular disease, and multivessel disease predicted MACE is in keeping with prior studies.33-40 However, SDOH also added incrementally to the predictive model. We found that being widowed (vs married or divorced) increased the risk of MACE, while having private insurance was associated with a protective effect. Of the PD patients, 50% were married, 17% divorced, 16% single, 13% were widowed, and 2.9% did not disclose this information. Compared with being married or divorced, widowhood conferred a 1.9- and 2.6-fold incremental risk of MACE, respectively. There was also a 1.4-fold increased risk of MACE in widowed patients compared with those who were single; however, this did not reach statistical significance and therefore did not remain in the model. Widowhood has also been shown to increase mortality from heart disease and multiple other causes.41,42 Major grief reactions, emotional stress, depression, and the loss of support associated with losing a spouse or partner may all contribute.41 Prior studies have also shown that insurance status may affect cardiovascular outcomes. Similar to our study, Gaglia et al43 reported lower MACE rates in patients under age 65 years who had private insurance compared with Medicaid, Medicare, or no insurance. These findings and ours suggest that clinical and angiographic factors and SDOH may all affect post-PCI outcomes. Accordingly, we encourage future PCI outcomes studies to collect and report data on SDOH in addition to conventional PCI risk factors.

There were other insights gained from studying SDOH. Compared with women, minorities had lower degrees of education, lower annual household income, and lower rates of having an established primary care physician. Minorities were also more likely to have a foreign language as their primary language and to experience language discordance between themselves and their physicians. Although minorities reported regular exercise more often than women, paradoxically they also had higher rates of obesity. Prior studies have shown that education, health literacy, language barriers, and insurance status all play an important role in patients’ compliance and outcome.44,45 Distance and accessibility to health care may also impact a patient’s choice of health care provider and outcome.46,47 In our study, even though minority patients often lived less than 30 minutes away from the treating hospital, these patients had slightly lower follow-up rates. The fairly common use of smartphones suggests that digital technology may be a useful tool to improve compliance and follow up.48-50 Insights from SDOH data may help clinicians formulate more race/ethnicity- and sex–specific programs to promote health, improve compliance, and reduce risk.

Study Limitations

As patients were pooled from 2 separate PCI studies (PD and PE Plus), we cannot exclude the effects of unrecognized biases. We felt it valid to combine them because all patients were treated in a similar timeframe with comparable platinum-chromium everolimus-eluting stents, both studies enrolled consecutive US patients across 52 sites, and outcomes were adjudicated at the same time by an independent clinical events committee and using identical end point definitions. Furthermore, our logistic regression model provided additional statistical validity for pooling (eTable 1 in the Supplement). The overall follow-up rate at 1 year was high (92%-95%) but not perfect. However, follow-up was still robust across groups and in keeping with other contemporary PCI studies. Information on SDOH and medication compliance was self-reported and therefore prone to recall bias. Specific details on diet and exercise were not collected. Our study was statistically powered for MACE but not for other secondary end points, raising the potential for beta error, especially for infrequently encountered events such as stent thrombosis.

Conclusions

Women and minorities undergoing contemporary PCI present with more comorbidities than white men but share a similar adjusted risk of 1-year MACE, death, and TVR. Women and minorities experience a greater adjusted risk of 1-year death/MI (and MI for minorities), driven predominantly by a higher risk of nonstent-related MI. Our data suggest that differential risks of thrombosis or atherosclerosis contribute more to this phenomenon than stent failure. The independent predictors of MACE in women and minorities were cardiogenic shock, renal disease, peripheral vascular disease, multivessel disease, widowhood, and lack of private insurance. In providing a comprehensive evaluation of the impact of race/ethnicity, sex, and SDOH on contemporary PCI outcomes, this study contributes significantly to our current knowledge base.

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Article Information

Corresponding Author: Wayne Batchelor, MD, MHS, Florida State University College of Medicine, Southern Medical Group, P.A., 1300 Medical Dr, Tallahassee, FL 32308 (wabat@southern-med.com).

Accepted for Publication: August 30, 2017.

Published Online: October 18, 2017. doi:10.1001/jamacardio.2017.3802

Author Contributions: Drs Batchelor and Mehran had access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Batchelor and Mehran contributed equally to the work.

Concept and design: Batchelor, Singh, Underwood, Thompson, Mehran.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Batchelor, Davis, Singh, Lopez, Chandrasekhar, Underwood, Mehran.

Critical revision of the manuscript for important intellectual content: Batchelor, Kandzari, Tami, Wang, Othman, Gigliotti, Haghighat, Singh, Giugliano, Horwitz, Underwood, Thompson, Mehran.

Statistical analysis: Batchelor.

Obtained funding: Batchelor.

Administrative, technical, or material support: Othman, Lopez, Underwood, Thompson.

Supervision: Batchelor, Kandzari, Singh, Underwood, Thompson, Mehran.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Batchelor reports institutional grant/research support from Boston Scientific and consulting for Abbott, Medtronic, and Boston Scientific. Dr Kandzari reports minor consulting honoraria from Medtronic, Boston Scientific, and Micell Technologies and research/grant support from Medtronic, Boston Scientific, Biotronik, and St. Jude Medical/Abbott. Dr Wang reports consultant/executive committee for Boston Scientific. Dr Horwitz reports grant support from Boston Scientific. Drs Underwood and Thompson are full-time employees and stock holders of Boston Scientific Corporation.Dr Mehran reports institutional grant/research support from Daiichi-Sankyo/Eli Lilly, Bristol-Myers Squibb, AstraZeneca, The Medicines Company, OrbusNeich, Bayer, CSL Behring, Abbott Laboratories, Watermark Research Partners, Novartis Pharmaceuticals Medtronic, AUM Cardiovascular, Beth Israel Deaconess Medical Center; consultant/executive committee for Janssen Pharmaceuticals, Osprey Medical, Watermark Research Partners, Medscape, The Medicines Company, Boston Scientific, Merck, Cardiovascular Systems, Sanofi USA, Shanghai BraccoSine Pharmaceutical, AstraZeneca (all minor); and equity for Claret Medical and Elixir Medical Corporation.

Additional Contributions: We thank all of the PLATINUM Diversity and PROMUS Element Plus Post-Approval Study investigators and sites for their invaluable contributions to this work. We also thank Kristine Roy, PhD (Boston Scientific Corporation), for assistance in manuscript preparation and Songtao Jiang, MSc, and Chuyu Deng, BSc (Boston Scientific Corporation), for assistance with statistical analysis. Dr Roy and Mr Jiang are full-time employees and stock holders of Boston Scientific Corporation. Ms Deng was an intern and received a salary from Boston Scientific Corporation at the time of manuscript submission.

References
1.
 2014 National population projections tables. United States Census Bureau. https://www.census.gov/data/tables/2014/demo/popproj/2014-summary-tables.html. Accessed September 11, 2017.
2.
Melloni  C, Berger  JS, Wang  TY,  et al.  Representation of women in randomized clinical trials of cardiovascular disease prevention.  Circ Cardiovasc Qual Outcomes. 2010;3(2):135-142.PubMedGoogle ScholarCrossref
3.
 Collection of race and ethnicity data in clinical trials. US Food and Drug Administration. https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126396.pdf. Accessed September 11, 2017.
4.
 NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research: amended, October, 2001. National Institutes of Health. https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. Accessed September 11, 2017.
5.
 Leading causes of death in males and females, United States. Centers for Disease Control and Prevention. https://www.cdc.gov/healthequity/lcod/index.htm. Accessed September 11, 2017.
6.
Maas  AH, van der Schouw  YT, Regitz-Zagrosek  V,  et al.  Red alert for women’s heart: the urgent need for more research and knowledge on cardiovascular disease in women: proceedings of the workshop held in Brussels on gender differences in cardiovascular disease, 29 September 2010.  Eur Heart J. 2011;32(11):1362-1368.PubMedGoogle ScholarCrossref
7.
Mody  P, Gupta  A, Bikdeli  B, Lampropulos  JF, Dharmarajan  K.  Most important articles on cardiovascular disease among racial and ethnic minorities.  Circ Cardiovasc Qual Outcomes. 2012;5(4):e33-e41.PubMedGoogle ScholarCrossref
8.
Argulian  E, Patel  AD, Abramson  JL,  et al.  Gender differences in short-term cardiovascular outcomes after percutaneous coronary interventions.  Am J Cardiol. 2006;98(1):48-53.PubMedGoogle ScholarCrossref
9.
Thompson  CA, Kaplan  AV, Friedman  BJ,  et al.  Gender-based differences of percutaneous coronary intervention in the drug-eluting stent era.  Catheter Cardiovasc Interv. 2006;67(1):25-31.PubMedGoogle ScholarCrossref
10.
Lansky  AJ, Costa  RA, Mooney  M,  et al; TAXUS-IV Investigators.  Gender-based outcomes after paclitaxel-eluting stent implantation in patients with coronary artery disease.  J Am Coll Cardiol. 2005;45(8):1180-1185.PubMedGoogle ScholarCrossref
11.
Akhter  N, Milford-Beland  S, Roe  MT, Piana  RN, Kao  J, Shroff  A.  Gender differences among patients with acute coronary syndromes undergoing percutaneous coronary intervention in the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR).  Am Heart J. 2009;157(1):141-148.PubMedGoogle ScholarCrossref
12.
Collins  SD, Torguson  R, Gaglia  MA  Jr,  et al.  Does black ethnicity influence the development of stent thrombosis in the drug-eluting stent era?  Circulation. 2010;122(11):1085-1090.PubMedGoogle ScholarCrossref
13.
Batchelor  WB, Ellis  SG, Ormiston  JA,  et al.  Racial differences in long-term outcomes after percutaneous coronary intervention with paclitaxel-eluting coronary stents.  J Interv Cardiol. 2013;26(1):49-57.PubMedGoogle ScholarCrossref
14.
Stefanini  GG, Baber  U, Windecker  S,  et al.  Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials.  Lancet. 2013;382(9908):1879-1888.PubMedGoogle ScholarCrossref
15.
Kandzari  DE, Amjadi  N, Caputo  C,  et al.  One-year outcomes in “real-world” patients treated with a thin-strut, platinum-chromium, everolimus-eluting stent (from the PROMUS Element Plus US Post-Approval Study [PE-Plus PAS]).  Am J Cardiol. 2016;117(4):539-545.PubMedGoogle ScholarCrossref
16.
World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.  JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053.Google ScholarCrossref
17.
Meredith  IT, Whitbourn  R, Scott  D,  et al.  PLATINUM QCA: a prospective, multicentre study assessing clinical, angiographic, and intravascular ultrasound outcomes with the novel platinum chromium thin-strut PROMUS Element everolimus-eluting stent in de novo coronary stenoses.  EuroIntervention. 2011;7(1):84-90.PubMedGoogle ScholarCrossref
18.
Stone  GW, Teirstein  PS, Meredith  IT,  et al; PLATINUM Trial Investigators.  A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: the PLATINUM (a Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of Up to Two de Novo Coronary Artery Lesions) trial.  J Am Coll Cardiol. 2011;57(16):1700-1708.PubMedGoogle ScholarCrossref
19.
Coakley  M, Fadiran  EO, Parrish  LJ, Griffith  RA, Weiss  E, Carter  C.  Dialogues on diversifying clinical trials: successful strategies for engaging women and minorities in clinical trials.  J Womens Health (Larchmt). 2012;21(7):713-716.PubMedGoogle ScholarCrossref
20.
Resnik  DB, Jones  CW.  Research subjects with limited English proficiency: ethical and legal issues.  Account Res. 2006;13(2):157-177.PubMedGoogle ScholarCrossref
21.
Nolan  MR, Nguyen  T-L.  Analysis and reporting of sex differences in phase III medical device clinical trials-how are we doing?  J Womens Health (Larchmt). 2013;22(5):399-401.PubMedGoogle ScholarCrossref
22.
Pinnow  E, Herz  N, Loyo-Berrios  N, Tarver  M.  Enrollment and monitoring of women in post-approval studies for medical devices mandated by the Food and Drug Administration.  J Womens Health (Larchmt). 2014;23(3):218-223.PubMedGoogle ScholarCrossref
23.
Dhruva  SS, Bero  LA, Redberg  RF.  Gender bias in studies for Food and Drug Administration premarket approval of cardiovascular devices.  Circ Cardiovasc Qual Outcomes. 2011;4(2):165-171.PubMedGoogle ScholarCrossref
24.
 FDASIA section 907: inclusion of demographic subgroups in clinical trials. US Food and Drug Administration. https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm389100.htm. Accessed September 11, 2017.
25.
Berger  JS, Melloni  C, Wang  TY,  et al.  Reporting and representation of race/ethnicity in published randomized trials.  Am Heart J. 2009;158(5):742-747.PubMedGoogle ScholarCrossref
26.
Kurt  A, Semler  L, Meyers  M, Porter  BG, Jacoby  JL, Stello  B.  Research professionals’ perspectives, barriers, and recommendations regarding minority participation in clinical trials [published online December 21, 2016].  J Racial Ethn Heal Disparities.Google Scholar
27.
Pradhan  J, Schreiber  TL, Niraj  A,  et al.  Comparison of five-year outcome in African Americans versus Caucasians following percutaneous coronary intervention.  Catheter Cardiovasc Interv. 2008;72(1):36-44.PubMedGoogle Scholar
28.
Gaglia  MAJ  Jr, Steinberg  DH, Pinto Slottow  TL,  et al.  Racial disparities in outcomes following percutaneous coronary intervention with drug-eluting stents.  Am J Cardiol. 2009;103(5):653-658.PubMedGoogle ScholarCrossref
29.
Kobayashi  T, Glorioso  TJ, Armstrong  EJ,  et al.  Comparative outcomes after percutaneous coronary intervention among black and white patients treated at US Veterans Affairs hospitals [published online July 19, 2017].  JAMA Cardiol. PubMedGoogle Scholar
30.
Kumar  RS, Douglas  PS, Peterson  ED,  et al.  Effect of race and ethnicity on outcomes with drug-eluting and bare metal stents: results in 423 965 patients in the linked National Cardiovascular Data Registry and centers for Medicare & Medicaid services payer databases.  Circulation. 2013;127(13):1395-1403.PubMedGoogle ScholarCrossref
31.
Gurbel  PA, Bliden  KP, Cohen  E,  et al.  Race and sex differences in thrombogenicity: risk of ischemic events following coronary stenting.  Blood Coagul Fibrinolysis. 2008;19(4):268-275.PubMedGoogle ScholarCrossref
32.
Mehran  R, Baber  U, Steg  PG,  et al.  Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study.  Lancet. 2013;382(9906):1714-1722.PubMedGoogle ScholarCrossref
33.
Awad  HH, Anderson  FA  Jr, Gore  JM, Goodman  SG, Goldberg  RJ.  Cardiogenic shock complicating acute coronary syndromes: insights from the Global Registry of Acute Coronary Events.  Am Heart J. 2012;163(6):963-971.PubMedGoogle ScholarCrossref
34.
Garot  P, Morice  MC, Tresukosol  D,  et al; LEADERS FREE Investigators.  2-Year outcomes of high bleeding risk patients after polymer-free drug-coated stents.  J Am Coll Cardiol. 2017;69(2):162-171.PubMedGoogle ScholarCrossref
35.
Gupta  R, Kirtane  AJ, Ozane  MO,  et al.  Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents in subjects with peripheral arterial disease: analysis from the ADAPT-DES Study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).  Circ Cardiovasc Interv. 2017;10(3):.Google Scholar
36.
Kang  J, Park  KW, Han  JK,  et al.  Usefulness of the baseline syntax score to predict 3-year outcome after complete revascularization by percutaneous coronary intervention.  Am J Cardiol. 2016;118(5):641-646.PubMedGoogle ScholarCrossref
37.
Kunadian  V, Qiu  W, Ludman  P,  et al; National Institute for Cardiovascular Outcomes Research.  Outcomes in patients with cardiogenic shock following percutaneous coronary intervention in the contemporary era: an analysis from the BCIS database (British Cardiovascular Intervention Society).  JACC Cardiovasc Interv. 2014;7(12):1374-1385.PubMedGoogle ScholarCrossref
38.
Lee  JM, Kang  J, Lee  E,  et al.  Chronic kidney disease in the second-generation drug-eluting stent era: pooled analysis of the Korean multicenter drug-eluting stent registry.  JACC Cardiovasc Interv. 2016;9(20):2097-2109.PubMedGoogle ScholarCrossref
39.
Lee  SY, Hong  MK, Shin  DH,  et al.  Association between duration of dual antiplatelet therapy and angiographic multivessel disease on outcomes in patients treated with newer-generation drug-eluting stents.  Circ Cardiovasc Interv. 2016;9(11):e004256.PubMedGoogle ScholarCrossref
40.
Secemsky  EA, Yeh  RW, Kereiakes  DJ,  et al; Dual Antiplatelet Therapy Study Investigators.  Extended duration dual antiplatelet therapy after coronary stenting among patients with peripheral arterial disease: a subanalysis of the Dual Antiplatelet Therapy Study.  JACC Cardiovasc Interv. 2017;10(9):942-954.PubMedGoogle ScholarCrossref
41.
Elwert  F, Christakis  NA.  The effect of widowhood on mortality by the causes of death of both spouses.  Am J Public Health. 2008;98(11):2092-2098.PubMedGoogle ScholarCrossref
42.
Moon  JR, Kondo  N, Glymour  MM, Subramanian  SV.  Widowhood and mortality: a meta-analysis.  PLoS One. 2011;6(8):e23465.PubMedGoogle ScholarCrossref
43.
Gaglia  MA  Jr, Torguson  R, Xue  Z,  et al.  Effect of insurance type on adverse cardiac events after percutaneous coronary intervention.  Am J Cardiol. 2011;107(5):675-680.PubMedGoogle ScholarCrossref
44.
Krueger  KP, Berger  BA, Felkey  B.  Medication adherence and persistence: a comprehensive review.  Adv Ther. 2005;22(4):313-356.PubMedGoogle ScholarCrossref
45.
Haynes  RB, McDonald  H, Garg  AX, Montague  P.  Interventions for helping patients to follow prescriptions for medications.  Cochrane Database Syst Rev. 2002;(2):CD000011.PubMedGoogle Scholar
46.
Cote  CL, Singh  S, Yip  AM,  et al.  Increased distance from the tertiary cardiac center is associated with worse 30-day outcomes after cardiac operations.  Ann Thorac Surg. 2015;100(6):2213-2218.PubMedGoogle ScholarCrossref
47.
Victoor  A, Delnoij  DM, Friele  RD, Rademakers  JJ.  Determinants of patient choice of healthcare providers: a scoping review.  BMC Health Serv Res. 2012;12(1):272.PubMedGoogle ScholarCrossref
48.
Palacio  AM, Uribe  C, Hazel-Fernandez  L,  et al.  Can phone-based motivational interviewing improve medication adherence to antiplatelet medications after a coronary stent among racial minorities? a randomized trial.  J Gen Intern Med. 2015;30(4):469-475.PubMedGoogle ScholarCrossref
49.
Free  C, Phillips  G, Watson  L,  et al.  The effectiveness of mobile-health technologies to improve health care service delivery processes: a systematic review and meta-analysis.  PLoS Med. 2013;10(1):e1001363.PubMedGoogle ScholarCrossref
50.
Lefebvre  RC, Bornkessel  AS.  Digital social networks and health.  Circulation. 2013;127(17):1829-1836.PubMedGoogle ScholarCrossref
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